Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors
Abstract
:1. Introduction
2. Rationale for the Combination of Cancer Vaccines AND Checkpoint Inhibitor Blockade
3. Combination of Cancer Vaccines and Modulation of Costimulatory Pathways in Preclinical Models (Table 1)
3.1. Inhibitory Pathway (PD-1/PD-L1-PD-L2, CTLA-4/CD80-CD86) Blockade Increases the Efficacy of Various Types of Cancer Vaccines
3.1.1. Peptide Vaccines
3.1.2. Live Vectors
3.1.3. Cellular Vaccines
3.1.4. Inert Vectors Targeting Dendritic Cells
3.1.5. DNA Vaccines
3.2. Synergy between Cancer Vaccines and Checkpoint Inhibitor Blockade Extends Beyond CTLA-4 and PD-1 Pathway Inhibition
3.3. Checkpoint Inhibitor Blockade is Not Limited to the Use of Antibodies
3.4. Agonist Antibodies Directed Against Costimulatory Molecules are also Synergistic with Cancer Vaccines
3.5. Multiple Targeting of Costimulatory or Inhibitory Receptors Dramatically Improved the Efficiency of Cancer Vaccines
3.5.1. Cancer Vaccines Combined with Multiple Inhibitory Receptor Blockade
3.5.2. Cancer Vaccines Combined with Agonist mAb Against Costimulatory Molecules and Antagonist mAb Against Checkpoint Inhibitors
4. Mechanisms Mediating the Efficacy of Cancer Vaccines Combined with Inhibitory Pathway Blockade or Costimulatory Pathway Activation
5. Combinations of Cancer Vaccine and Modulation of Inhibitory Pathways in Humans
6. Conclusions and Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Type of Checkpoint Inhibitor Blocked | Type of Tumor | Type of Vaccine | Clinical Benefit and Toxicity | Ref. |
---|---|---|---|---|
Anti-CTLA-4 | SM1 cell line (mammary tumor) | 1 × 106 irradiated GM-CSF transduced SM1 cells (s.c.) | Complete regression of tumor volume and enhanced survival of mice | [52] |
B16-BL6 cell line (melanoma) | 1 × 106 irradiated GM-CSF–producing B16-BL6 and B16-F10 (sc) | Eradication of established tumors in 80% (68/85) of the cases. Development of depigmentation, starting at the site of vaccination or challenge and in most cases progressing to distant sites. | [53] | |
TRAMP-C2 cell line (prostate cancer) | 1 × 106 cells irradiated GMTRAMP-C1/C2 | Reduction in tumor incidence and tumor grade. Development of prostatitis accompanied by destruction of glandular epithelium of the male reproductive tract | [54] | |
SP1 cell line (Prostate cancer) | GVAX: 1 × 106 TRMPC-2HA admixed with 5 × 104 B78H1-GM then irradiated | Dramatic increase in effector CD8+T cells in the prostate gland, and enhanced tumor-antigen directed lytic function and decreased tumor burden and histologic grade in ProHA × TRAMP mice | [55] | |
B16/BL6 (melanoma TRAMP-C2 cell line (prostate cancer) | Fl3vax: irradiated 1 × 106 Flt3L-expressing B16/BL6 (i.d.) | Rejection of established TRAMP prostate adenocarcinomas. Significantly greater prevention of the outgrowth of 5-day implanted B16-BL6 tumors than Gvax | [56] | |
B16 cell line (Melanoma) | Synthetic peptide+ CpG-ODN adjuvant | Increased survival of mice with poorly immunogenic B16 melanoma in a therapeutic protocol, but ineffective in the prophylactic mode. | [57] | |
11A-1 & MC-38 cell line (mammary and colon carcinoma | Modified vaccinia Ankara-expressing murine p53 +CpG-ODN | The combination of CpG ODN and CTLA-4 blockade synergized for the rejection of palpable 11A-1 and MC-38 tumors | [58] | |
EG7-OVA cells (Thymoma) | 2 × 106 SIINFEKL-pulsed or unpulsed DCs (i.d.) | Rejection or slowed tumor growth in more than 60% of mice. | [59] | |
CT26 cells (Colon cancer) | 106 cells peptide pulsed DCs (i.d.) | Increased mean survival of mice. | [60] | |
MC-38 (Colon cancer) | 2–3 × 105 cells peptide pulsed DCs (i.d.) | Improvement of tumor-free survival of mice Immunized mice appeared healthy and maintained normal weight compared to mice mock-vaccinated with PBS. | [61] | |
Meth A cells (Sarcoma) | Modified vaccinia Ankara (MVA) poxvirus encoding mutated p53 protein vaccine (i.p.) | Improvement of tumor-free survival (11/14) of mice receiving combination therapy | [62] | |
MC-38 cells expressing CEA (Colon cancer) | 1 × 107 recombinant vaccinia vector carrying the genes for CEA, B7.1, ICAM-1, and LFA-3 | Reduction of tumor volume complete eradication of the tumor (4 out of 20 mice). No signs of autoimmunity | [63] | |
Anti-CTLA-4 + anti-PD-1 | B16-BL6 cells (Melanoma) | 1 × 106 B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) | Reduction of tumor volume enhanced survival (75% survival with combined regimen versus 25% with monotherapy) | [64] |
CT26 cell line & ID8-VEGF cell line (colon and ovarian cancer) | 1 × 106 irradiated (150Gy) CT26-GVAX or ID8-VEGF-GVAX | Reduction of tumor volume and increased tumor rejection (between 75%–100% of tumor-free mice with combined therapy versus 30%–50% with monotherapy) | [65] | |
B16-OVA cell line (melanoma) | Bacterial vaccine: The leucine–arginine auxotrophic S. Typhimurium A1-R strain 2 x 107 colony formation units | Eradication of established tumor in 80% of mice receiving the combined regimen | [66] | |
anti-CTLA-4 + anti-OX40 | TUBO cell line (Breast cancer) | Anti–DEC-205/HER2 monoclonal antibodies | 4-fold reduction of tumor volume and survival enhancement (40% survival versus 0%) | [67] |
Anti-PDL-1 | ID8 cell line (i.p.) (Ovarian cancer) | 106 irradiated ID8 cells expressing murine GM-CSF (ID8-GVAX) or Flt3-ligand (ID8-FVAX) | Rejection of ID8 tumor in 75% of tumor bearing mice increased proliferation and function of tumor antigen CD8+T cells | [65] |
MDA-MB-231 & MDA-MB-435 (breast cancer) | DC vaccine | Reduction of tumor volume and enhanced survival (60% of mice survived in the groups treated with DC vaccines versus 100% mortality with vaccine alone or anti-PDL1 alone) | [68] | |
anti-PD-1 | B16F10, EL4, RMA-S cells (melanoma, thymoma, lymphoma) | DC vaccine+Poly-IC+anti-CD40 (Trivax) | Eradication of established tumor enhanced survival | [61] |
B16 cell line (melanoma) | A tumor cell based vaccine to create TLR agonists (TEGVAX) | Reduction of tumor volume (50% regression) appearance of vitiligo after treatment | [69] | |
TC-1 cell line (lung cancer) | vaccine (E7/GM-CSF/anti-CD40) | Reduction of tumor volume (10-fold reduction) and enhanced survival (50%) | [70] | |
CD27 agonist + anti-PD-1 | TC-1 cell line (lung cancer) | HELP-E7SH & E7SH DNA vaccines | Eradication of established tumor, resulting in 100% survival of the mice treated with combined therapy | [71] |
Anti-BTLA | Transgenic mouse model mimicking thyroid adenocarcinoma | E7 expressed by herpes simplex virus (HSV)-1 glycoprotein D (gD) | Slowing of tumor progression resulting in 50% reduction of thyroid weight | [72] |
VISTA blockade | B16-BL6 cells (melanoma) | Peptide-based cancer vaccine with TLR agonists as adjuvants | Eradication of established tumor protection against tumor rechallenge in 50% of mice | [73] |
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Karaki, S.; Anson, M.; Tran, T.; Giusti, D.; Blanc, C.; Oudard, S.; Tartour, E. Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors. Vaccines 2016, 4, 37. https://doi.org/10.3390/vaccines4040037
Karaki S, Anson M, Tran T, Giusti D, Blanc C, Oudard S, Tartour E. Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors. Vaccines. 2016; 4(4):37. https://doi.org/10.3390/vaccines4040037
Chicago/Turabian StyleKaraki, Soumaya, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, and Eric Tartour. 2016. "Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors" Vaccines 4, no. 4: 37. https://doi.org/10.3390/vaccines4040037